Emerging drug profile: menin inhibitors in NPM1-mutated and KM2A-rearranged acute myeloid leukemia

Understanding the clinical significance of genetic aberrations in acute myeloid leukemia (AML) has led to the development of several specific treatment drugs that have improved clinical outcomes. Recently, several clinical trials have investigated new therapeutic drugs in this context, either alone or in combination with intensive chemotherapy or low-intensity treatments. Among these, menin inhibitors may constitute a new class of targeted treatments for AML caused by mutations in the nucleophosmin 1 (NPM1) gene or rearrangement of the lysine methyltransferase 2 A (KMT2A) gene. Within the class of menin inhibitors, revumenib is the FDA-approved therapy for the R/R AML with NPM1 mutations, as well as for KMT2A gene rearrangements, which received approval in the year 2025 and 2024, respectively. In addition, ziftomenib got approval in 2025 for patients with R/R AML with NPM1 mutations who lack satisfactory alternative treatment options. Currently, several small-molecule menin inhibitors are being tested in combination with conventional therapies. This publication reviews the recent progress in investigating the clinical evidence of menin inhibitors (revumenib, ziftomenib, bleximenib, enzomenib, BMF-219, emilumenib) toward aggressive leukemias, guides future study and optimal treatment for patients with this type of leukemia.